• Title/Summary/Keyword: Tumor burden

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Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

  • Yeong, Looi Ting;Hamid, Roslida Abdul;Yazan, Latifah Saiful;Khaza'ai, Huzwah
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2301-2305
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    • 2013
  • Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA, $100{\mu}g/100{\mu}l$) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume ($8.79{\pm}5.44$) and tumor burden ($3.60{\pm}1.17$). Comparatively, group III revealed only 20% of tumor incidence, tumor burden ($3.00{\pm}1.00$) and tumor volume ($2.40{\pm}1.12$), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.

Strategies for Appropriate Patient-centered Care to Decrease the Nationwide Cost of Cancers in Korea (국가 암 비용 감소를 위한 환자중심 진료의 적정성 확보 전략)

  • Bae, Jong-Myon
    • Journal of Preventive Medicine and Public Health
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    • v.50 no.4
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    • pp.217-227
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    • 2017
  • In terms of years of life lost to premature mortality, cancer imposes the highest burden in Korea. In order to reduce the burden of cancer, the Korean government has implemented cancer control programs aiming to reduce cancer incidence, to increase survival rates, and to decrease cancer mortality. However, these programs may paradoxically increase the cost burden. For examples, a cancer screening program for early detection could bring about over-diagnosis and over-treatment, and supplying medical services in a paternalistic manner could lead to defensive medicine or futile care. As a practical measure to reduce the cost burden of cancer, appropriate cancer care should be established. Ensuring appropriateness requires patient-doctor communication to ensure that utility values are shared and that autonomous decisions are made regarding medical services. Thus, strategies for reducing the cost burden of cancer through ensuring appropriate patient-centered care include introducing value-based medicine, conducting cost-utility studies, and developing patient decision aids.

Paired analysis of tumor mutation burden calculated by targeted deep sequencing panel and whole exome sequencing in non-small cell lung cancer

  • Park, Sehhoon;Lee, Chung;Ku, Bo Mi;Kim, Minjae;Park, Woong-Yang;Kim, Nayoung K.D.;Ahn, Myung-Ju
    • BMB Reports
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    • v.54 no.7
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    • pp.386-391
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    • 2021
  • Owing to rapid advancements in NGS (next generation sequencing), genomic alteration is now considered an essential predictive biomarkers that impact the treatment decision in many cases of cancer. Among the various predictive biomarkers, tumor mutation burden (TMB) was identified by NGS and was considered to be useful in predicting a clinical response in cancer cases treated by immunotherapy. In this study, we directly compared the lab-developed-test (LDT) results by target sequencing panel, K-MASTER panel v3.0 and whole-exome sequencing (WES) to evaluate the concordance of TMB. As an initial step, the reference materials (n = 3) with known TMB status were used as an exploratory test. To validate and evaluate TMB, we used one hundred samples that were acquired from surgically resected tissues of non-small cell lung cancer (NSCLC) patients. The TMB of each sample was tested by using both LDT and WES methods, which extracted the DNA from samples at the same time. In addition, we evaluated the impact of capture region, which might lead to different values of TMB; the evaluation of capture region was based on the size of NGS and target sequencing panels. In this pilot study, TMB was evaluated by LDT and WES by using duplicated reference samples; the results of TMB showed high concordance rate (R2 = 0.887). This was also reflected in clinical samples (n = 100), which showed R2 of 0.71. The difference between the coding sequence ratio (3.49%) and the ratio of mutations (4.8%) indicated that the LDT panel identified a relatively higher number of mutations. It was feasible to calculate TMB with LDT panel, which can be useful in clinical practice. Furthermore, a customized approach must be developed for calculating TMB, which differs according to cancer types and specific clinical settings.

Association between High Diffusion-Weighted Imaging-Derived Functional Tumor Burden of Peritoneal Carcinomatosis and Overall Survival in Patients with Advanced Ovarian Carcinoma

  • He An;Jose AU Perucho;Keith WH Chiu;Edward S Hui;Mandy MY Chu;Siew Fei Ngu;Hextan YS Ngan;Elaine YP Lee
    • Korean Journal of Radiology
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    • v.23 no.5
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    • pp.539-547
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    • 2022
  • Objective: To investigate the association between functional tumor burden of peritoneal carcinomatosis (PC) derived from diffusion-weighted imaging (DWI) and overall survival in patients with advanced ovarian carcinoma (OC). Materials and Methods: This prospective study was approved by the local research ethics committee, and informed consent was obtained. Fifty patients (mean age ± standard deviation, 57 ± 12 years) with stage III-IV OC scheduled for primary or interval debulking surgery (IDS) were recruited between June 2016 and December 2021. DWI (b values: 0, 400, and 800 s/mm2) was acquired with a 16-channel phased-array torso coil. The functional PC burden on DWI was derived based on K-means clustering to discard fat, air, and normal tissue. A score similar to the surgical peritoneal cancer index was assigned to each abdominopelvic region, with additional scores assigned to the involvement of critical sites, denoted as the functional peritoneal cancer index (fPCI). The apparent diffusion coefficient (ADC) of the largest lesion was calculated. Patients were dichotomized by immediate surgical outcome into high- and low-risk groups (with and without residual disease, respectively) with subsequent survival analysis using the Kaplan-Meier curve and log-rank test. Multivariable Cox proportional hazards regression was used to evaluate the association between DWI-derived results and overall survival. Results: Fifteen (30.0%) patients underwent primary debulking surgery, and 35 (70.0%) patients received neoadjuvant chemotherapy followed by IDS. Complete tumor debulking was achieved in 32 patients. Patients with residual disease after debulking surgery had reduced overall survival (p = 0.043). The fPCI/ADC was negatively associated with overall survival when accounted for clinicopathological information with a hazard ratio of 1.254 for high fPCI/ADC (95% confidence interval, 1.007-1.560; p = 0.043). Conclusion: A high DWI-derived functional tumor burden was associated with decreased overall survival in patients with advanced OC.

The CD28-B7 Family in Anti-Tumor Immunity: Emerging Concepts in Cancer Immunotherapy

  • Leung, Joanne;Suh, Woong-Kyung
    • IMMUNE NETWORK
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    • v.14 no.6
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    • pp.265-276
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    • 2014
  • The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.

Proteomic Analysis of Serum of Women with Elevated Ca-125 to Differentiate Malignant from Benign Ovarian Tumors

  • Li, Li;Xu, Yi;Yu, Chun-Xia
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3265-3270
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    • 2012
  • Clinically, elevated cancer antigen 125 (CA-125) in blood predicts tumor burden in a woman's body, especially in the ovary, but cannot differentiate between malignant or benign. We here used intensive modern proteomic approaches to identify predictive proteins in the serum of women with elevated CA-125 to differentiate malignant from benign ovarian tumors. We identified differentially expressed proteins in serum samples of ovarian cancer (OC) patients, benign ovarian tumor (BT) patients, and healthy control women using mass spectrometry-based quantitative proteomics. Both the OC and BT patients had elevated CA-125. Quantitation was achieved using isobaric tags for relative and absolute quantitation. We obtained 124 quantified differential serum proteins in OC compared with BT. Two proteins, apolipoprotein A-4 (APOA4) and natural resistance-associated macrophage 1, were verified using Western blotting. Proteome profiling applied to OC cases identified several differential serum proteins in the serum of women with elevated CA-125. A novel protein, APOA4, has the potential to be a marker for malignant tumor differentiation in the serum of women with elevated CA-125.

In Vivo Antitumor Efficacy of Cw252053, A Folate-based Thymidylate Synthase Inhibitor

  • Oh, Se-Woong;Ha, Jong-Ryul;Baek, Du-Jong
    • Archives of Pharmacal Research
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    • v.24 no.4
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    • pp.323-326
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    • 2001
  • Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this studys, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F$_1$ mice were injected with LY3.7. 2C TK-/- (thymidine kinase deficient mouse Iymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30mgmg/kg CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rat against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

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Circulating Tumor Cell Number Is Associated with Primary Tumor Volume in Patients with Lung Adenocarcinoma

  • Kang, Byung Ju;Ra, Seung Won;Lee, Kyusang;Lim, Soyeoun;Son, So Hee;Ahn, Jong-Joon;Kim, Byung Chul
    • Tuberculosis and Respiratory Diseases
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    • v.83 no.1
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    • pp.61-70
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    • 2020
  • Background: Circulating tumor cells (CTCs) are frequently detected in patients with advanced-stage malignant tumors and could act as a predictor of poor prognosis. However, there is a paucity of data on the relationship between CTC number and primary tumor volume in patients with lung cancer. Therefore, our study aimed to evaluate the relationship between CTC number and primary tumor volume in patients with lung adenocarcinoma. Methods: We collected blood samples from 21 patients with treatment-naive lung adenocarcinoma and 73 healthy individuals. To count CTCs, we used a CTC enrichment method based on fluid-assisted separation technology. We compared CTC numbers between lung adenocarcinoma patients and healthy individuals using propensity score matching, and performed linear regression analysis to analyze the relationship between CTC number and primary tumor volume in lung adenocarcinoma patients. Results: CTC positivity was significantly more common in lung adenocarcinoma patients than in healthy individuals (p<0.001). The median primary tumor volume in CTC-negative and CTC-positive patients was 10.0 ㎤ and 64.8 ㎤, respectively. Multiple linear regression analysis showed that the number of CTCs correlated with primary tumor volume in lung adenocarcinoma patients (β=0.903, p=0.002). Further subgroup analysis showed a correlation between CTC number and primary tumor volume in patients with distant (p=0.024) and extra-thoracic (p=0.033) metastasis (not in patients with distant metastasis). Conclusion: Our study showed that CTC numbers may be associated with primary tumor volume in lung adenocarcinomas patients, especially in those with distant metastasis.

Tumor lysis syndrome following sorafenib treatment in hepatocellular carcinoma

  • Kim, Shin Young;Kim, Hee Yeon;Kim, Yu Seung;Lee, Sang Min;Kim, Chang Wook
    • Journal of Yeungnam Medical Science
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    • v.32 no.1
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    • pp.47-49
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    • 2015
  • Sorafenib is indicated for the treatment of advanced hepatocellular carcinoma (HCC), but although rare, tumor lysis syndrome (TLS) can be fatal in HCC patients with a large tumor burden. The authors describe the case of a 55-year-old hepatitis B carrier who visited our clinic with progressive dyspnea for 3 weeks. Chest and abdominal computed tomography revealed a huge HCC in the left lobe of the liver with invasion of the inferior vena cava, right atrium, and pulmonary arteries. After 8 days of sorafenib administration, TLS was diagnosed based on the characteristic findings of hyperuricemia, hyperkalemia, and acute kidney injury with massive tumor necrosis by follow-up imaging. Despite discontinuation of sorafenib and supportive care, the patient's clinical course rapidly deteriorated. The authors describe a rare but fatal complication that occurred soon after sorafenib initiation for HCC. Careful follow-up is required after commencing sorafenib therapy for the early diagnosis and management of TLS.

Recurrence Analysis of Giant Cell Tumor after Curettage and Cementation (거대 세포종에서 골 소파술 및 시멘트 충전술 후의 재발 분석)

  • Hahn, Soo-Bong;Lee, Won-Jun;Shin, Kyoo-Ho
    • The Journal of the Korean bone and joint tumor society
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    • v.10 no.2
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    • pp.71-78
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    • 2004
  • Purpose: The purpose of this study is to investigate the characteristic of recurred giant cell tumor after bony curettage and cementation, and to review a way to prevent the recurrence. Materials and Methods : Thirty seven cases were analyzed, which were pathologically diagnosed giant cell tumor after diagnostic biopsy or surgical excision, followed by curative curettage, burring and cementation. Location, character, and time interval to recurrence were reviewed. Results: Thirteen out of thirty seven analyzed cases(35%) showed recurrence after primary curettage and cementation. The mean interval to recurrence was sixteen months(5 months to 43 months). Most of recurrence happened within the first two years except two cases. Among the recurred cases, eleven showed recurrence in the vicinity of window area. Two cases recurred in the depth of bone marrow, where cementation was made. The advantage of curettage and cementation is the immediate stability of the operation site, early rehabilitation, and early detection of recurrence. Furthermore, cementation is beneficial in that the cement-producing heat can eradicate the residual tumor burden. In this study, 85% of cases with insufficient curettage (for example, in cases where too small surgical window was made, or where there were anatomical difficulty in approaching the target tumor burden) showed recurrence. Conclusion: Bony curettage, burring and cementation is widely used as the primary curative modality for giant cell tumor. A few other modalities such as chemical cautery using phenol and $H_2O_2$; cryotherapy; and anhydroalcohol have also been introduced, but the benefit of these are still questionable. For some cases that relatively small surgical window was made due to anatomically complicated structures (such as ligament insertion or origin site) over the target tumor burden, unsatisfactory curettage and burring was made. This study showed high chance of recurrence after unsatisfactory curettage, and 85% of recurrence developed in the vicinity of the small window area. Most of the recurrence occurred within the first two years. It is concluded that sufficient window opening, extensive curettage and eradicative burring are key factors to prevent recurrence. Also, it should be reminded that careful and close observation should be made for at least the first two years after initial treatment for early detection of recurrence.

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